Analysis of NSL knockout brains
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA577934 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:In the current study, we analyse the function of MOF-NSL complex in neural cells. We find that the NSL complex regulates metabolic networks in the brain.
2020-03-31 | GSE138981 | GEO
Project description:Mutations in the DJ-1 (Park7) gene cause autosomal recessive Parkinson's disease in humans, but the function of the DJ-1 protein is poorly characterized. In an effort to understand more about the biology of DJ-1, we performed iTRAQ analyses on subcellular fractions enriched from DJ-1 knockout rat and mouse brains. We generated iTRAQ datasets for mitochondria and cytosol enriched fractions from 6-month-old rat brains, and the cytosol enriched fraction from 14-15-month old mouse brains. Our subsequent analyses of these datasets led to our discovery that the Hexokinase 1 protein was increased in the cytosol components of both DJ-1 knockout species.
2017-10-04 | PXD005215 | Pride
Project description:We analyzed metabolites in the brains of wild type mice and DJ-1 knockout mice. The DJ-1 knockout mouse is a model of an inherited form of Parkinson's disease.
2015-09-17 | ST000260 | MetabolomicsWorkbench
Project description:The human males absent on the first (MOF)-containing non-specific lethal (NSL) histone acetyltransferase complex consists of 9 subunits can acetylate histone H4K16, H4K5 and H4K8. NSL complex is essential for the multiple transcriptional regulation mechanisms. In this work, mRNA profiles of WT and NSL3 knockout 293T cells were generated by deep sequencing, in triplicate. qRT–PCR validation was performed using SYBR Green assays. we identified more than 100 genes as NSL complex transcriptional targets, including several transcription factors (TFs), such as Yin Yang 1 (YY1) which are mainly involved in cell proliferation, biological adhesion, and metabolic processes. the NSL complex regulates gene expression by forming a gene regulatory network with multiple TFs. It is conceivable that the NSL complex participates in the regulation of a variety of biological functions in cells.
2022-03-18 | GSE198646 | GEO
Project description:The human males absent on the first (MOF)-containing non-specific lethal (NSL) histone acetyltransferase complex consists of 9 subunits can acetylate histone H4K16, H4K5 and H4K8. It has been known that this complex shares WDR5 subunit with the MLL/SET histone methyltransferases, suggesting that NSL complex is essential for the multiple transcriptional regulation mechanisms. However, there are few reports on the function of NSL HAT in genome, It is necessary to clarify the details and specificity of histone H4 acetylation cooperates with H3K4 methylation to regulate gene transcription. In this work, Our results show that The NSL complex plays a critical role in regulating multiple histone modifications by using the CRISPR/Cas9 NSL3-KO 293T cell line and ChIP-Seq approach. The global levels of highly enriched H4K16ac, H4K5ac, H3K4me2 and H3K4me3 at TSSs (TSS ± 3 kb region) are inhibited by NSL3-KO. NSL3-KO seemed to have little effect on the enhancer mark H3K27ac and repressor mark H3K27me3, but H3K4me1 was greatly affected by NSL3-KO. Moreover, the NSL complex govern gene transcription and identified genes by a coordinative mode of H4K16ac and H3K4me2/me3. What’s more, De novo motif analysis of MOF and NSL3 targets indicated that the NSL complex forms a gene regulatory network with multiple transcription factors by regulating their genes expression or cooperating with some factors through binding to specific motif.
2022-03-18 | GSE198645 | GEO
Project description:Mutations in the DJ-1 gene cause rare forms of autosomal recessive Parkinson's disease in humans. Recently, DJ-1 knockout rats have been generated and they have been reported to have subtle motor defects and neurodegeneration. We hypothesized that measuring the differences in mRNA expression in the brains of wildtype and DJ-1 knockout rats would provide insight into the mechanisms underlying these phenotypes. Using RNA-Seq, we were able to measure differential expression of over 2,000 genes in the DJ-1 knockout rat brains.
2017-09-11 | GSE71968 | GEO
Project description:The methyl lysine readers PHF (plant homeodomain finger) 20 (PHF20) and its homolog PHF20 Like 1 (PHF20L1) are known components of the NSL (non-specific lethal) complex that regulates gene expression through its histone acetyltransferase activity. In the current model, both PHF homologs coexist in the same NSL complex although this was not formally tested; nor have the functions of PHF20 and PHF20L1 regarding NSL complex integrity and transcriptional regulation been investigated. By performing an in-depth biochemical and functional characterization, we define the association and contributions of the two methyl lysine reader homologs PHF20 and PHF20L1 to the NSL complex.
2022-04-04 | PXD029258 | Pride
Project description:The methyl lysine readers PHF (plant homeodomain finger) 20 (PHF20) and its homolog PHF20 Like 1 (PHF20L1) are known components of the NSL (non-specific lethal) complex that regulates gene expression through its histone acetyltransferase activity. In the current model, both PHF homologs coexist in the same NSL complex although this was not formally tested; nor have the functions of PHF20 and PHF20L1 regarding NSL complex integrity and transcriptional regulation been investigated. Here we perform an in-depth biochemical and functional characterization of PHF20 and PHF20L1 in the context of the NSL complex. We identify the existence of two distinct NSL complexes that exclusively contain either PHF20 or PHF20L1; the two PHF homologs do not complex together in the same NSL species. Our data show that the C-terminal domains are essential for PHF20 and PHF20L1 to complex with NSL and the Tudor 2 domains of PHF20 and PHF20L1 are required for chromatin binding. The genome-wide landscape of PHF20/PHF20L1 binding to chromatin shows that they bind mostly to the same genomic regions, at promoters of highly expressed/housekeeping genes. Yet, deletion of PHF20 and PHF20L1 does not abrogate gene expression of the identified targets or impact the recruitment of NSL to the promoters of those genes, suggesting the existence of an alternative mechanism that compensates for the transcription of genes whose sustained expression is important for critical cellular functions.
2022-03-02 | GSE188601 | GEO
Project description:Cells rely on a diverse repertoire of genes for maintaining homeostasis, but the transcriptional networks underlying their expression remain poorly understood. The MOF acetyltransferase-containing Non-Specific Lethal (NSL) complex is a broad transcription regulator. It is essential in Drosophila and haploinsufficiency of the human KANSL1 subunit results in the Koolen-de Vries syndrome. Here, we perform a genome-wide RNAi screen and identify the BET protein BRD4 as evolutionary conserved co-factor of the NSL complex. Using Drosophila and mouse embryonic stem cells, we characterise a recruitment hierarchy, where NSL-deposited histone acetylation induces BRD4 recruitment for transcription of constitutively active genes. Transcriptome analyses in Koolen-de Vries patient-derived fibroblasts reveals perturbations with a cellular homeostasis signature that are evoked by the NSL complex/BRD4-axis. We propose that BRD4 represents a conserved bridge between the NSL complex and transcription activation and provide a new perspective in the understanding of their functions in healthy and diseased states.
2020-03-13 | GSE135771 | GEO
Project description:Loss of function mutations in the transcription factor THAP1 cause DYT6 dystonia, a childhood-onset motor disorder. DYT6 subjects display abnormalities in the white matter regions of the brain. Here, we generated conditional THAP1 knockout mice and analyzed the gene expression profiles from motor regions of mice brains to identify a role for THAP1 in the control of myelination
2017-07-10 | GSE97372 | GEO